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A breakthrough in Parkinson's. Copyright © 2018 NOS Life Sciences Corp. - All rights reserved. This document contains proprietary and confidential information of NOS Life Sciences Corp. The contents of this document may not be disclosed to third parties or duplicated in any form, in whole or in part, without prior written permission.
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !2
Imagine increasingly losing the ability to move, sleep, or smile.
While being completely aware of what is happening.
This is what Parkinson’s Disease can feel like.
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !3
Parkinson’s Disease is a neurodegenerative condition that progressively takes away the ability to move.
Problem (1/2)
Time
Autonomy / Motor Functionality
Y2 Y5 Y12Onset
• Nearly Normal
• Partial autonomy • Reduced work
capacity
• Severely Impaired • Caretaker needed • Cannot work
• Total dependance
Parkinson’s Disease Progression
Average years in disease progression.
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !4
Gold-standard treatment (Levodopa) helps to partially recover movement but presents critical unmet needs.
• Only partial recovery of movement.
• Causes Dyskinesia -permanent uncontrollable movements- which leads: - to a diminished autonomy / ability to function - to eventually stop treatment, leaving patients prostrated.
• Does not stop disease progression
Levodopa Limitations
Problem (2/2)
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !5
Lipea®: a breakthrough add-on therapy that would significantly increase patient quality of life.
• Enhancement of movement recovery by 100%*;
• Reduction of dyskinesia by 48%*; allowing for: - a better quality of life - added years of life with autonomy (i.e. extended
Levodopa therapeutic lifespan)
• Deceleration of disease progression by 79%*.
Solution (1/3)
Sources: (1) Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014),
17, 455–468. (2) Ramiro González-Aparicio et al. OEA reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson ́s disease. Neurobiology of Disease 62 (2014), 416–425.
Patient Benefit Goals
* As observed in pre-clinical trials.
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !6
Solution (2/3)
A highly effective therapeutic with no side-effects registered to date.
Key cellular signaling molecules and pathways: a) TPRV1 membrane receptors b) PPAR-alpha receptor c) MAPK - signaling pathways d) GPR119 membrane receptors
Mechanism of Action
Neuroprotective Action
Anti-dyskinetic Action
Description Lipea® is a pharmaceutically optimized formulation of OEA, an endogenous neuromodulator.
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !7
Less side effects will allow Levodopa to be dosed for more years,
also improving patients’ lives.
Reduced dyskinesia, will allow doctors to increase
Levodopa dose and improve patient’s quality
of life.
These patients end up prostrate with no available
options.
Dyskinesia causes many patients to ultimately abandon Levodopa
treatment.
Solution (3/3)
Patients will benefit from optimized, extended use of Levodopa with Lipea®.
Sources: (1) Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014),
17, 455–468. (2) Ramiro González-Aparicio et al. OEA reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson ́s disease. Neurobiology of Disease 62 (2014), 416–425.
Dyskinesia Reduction (2): • Axial dyskinesia: -48% • Forelimb dyskinesia: -50% • Orolingual dyskinesia: -48% • Contralateral rotations: -50%
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !8
100% improvement in motor functionality and 48% reduction of motor side effects are demonstrated by pre-clinical studies.
Pre-Clinical Results (1/3)
Enhancement of Motor Functionality (1): • Distance: +100% • Speed: +100% • Coordination: 140%
Sources: (1) Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014),
17, 455–468. (2) Ramiro González-Aparicio et al. OEA reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson ́s disease. Neurobiology of Disease 62 (2014), 416–425.
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !9
79% deceleration in disease progression is confirmed by Parkinson's pre-clinical study.
(1) Measured by TH+ cell quantity. Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014), 17, 455–468.
(2) Measured by TH+ cell density. Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014), 17, 455–468.
Pre-Clinical Results (2/3)
Protects Dopaminergic Neuron Health (2)
99%
Preserves Dopaminergic Neuron Quantity (1)
79%
Parkinson’s Disease constantly attacks and weakens
Dopaminergic Neurons. Eventually, they die.
Body Movement is controlled by Dopaminergic Neurons
• Lipea reaches the brain • Lipea is effective during the entire
duration of dyskinesia symptoms • Lipea is neuroprotective • No toxicity detected • No adverse effects detected • No “wearing-off” detected
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Lipea® meets crucial requirements for an effective long-term therapy, as substantiated in pre-clinical studies.
Sources: Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014), 17, 455–468. Ramiro González-Aparicio et al. OEA reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson ́s disease. Neurobiology of Disease 62 (2014), 416–425. Suardiaz et al - Analgesic properties of oleoylethanolamide (OEA) in visceral and inflammatory pain - Pain (2007) Anton et al - OEA prevents neuroimmune HMGB1/TLR4/NF-kB danger signalling in rat frontal cortex and depressive-like behaviour induced by ethanol binge administration - Addiction Biology (2016)
Pre-Clinical Results (3/3)
An effective long-term therapy
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !11
PD currently affects 13M people worldwide and, due to an aging population, is estimated to affect 32M by 2050.
• 32M by 2050 • Average onset age: 50 • As early as 25
13 M patients worldwide
• US: $26 Bn • Spain: $6.4 Bn • UK: $2.5 Bn
$120 Bn burden
Every hour, 85 people in the world are diagnosed with Parkinson’s disease.
85 new diagnosis per hour
Sources: - Willis AW, et al. (2010). Geographic and ethnic variation in Parkinson disease: a population- based study of US Medicare beneficiaries. Neuroepidemiology; 34: 143–151 - Marras C, Tanner CM. Epidemiology of Parkinson’s disease. In: Watts RL, Koller WC, eds. Movement disorders, neurologic principles and practice, 2nd ed. New York, McGraw Hill, 2004:177–196 - de Lau L and Breteler M. Epidemiology of Parkinson’s disease. Lancet Neurology 2006; 5: 525–35 - Huse DM, Schulman K, Orsini L, et al. Burden of illness in Parkinson's disease. Mov Disord. 2005;20:1449-1454. - Kowal SL, The current and projected economic burden of Parkinson's disease in the United States. Movement Disorder Society Official Journey 2013. - Willis AW, et al. (2010). Geographic and ethnic variation in Parkinson disease: a population- based study of US Medicare beneficiaries. Neuroepidemiology; 34: 143–151. - The social impact of Parkinson’s disease in Spain: Report by the Spanish Foundation for the Brain. Neurologia, 2016. - Gumber A et al, Economic, Social and Financial Cost of Parkinson's on Individuals, Carers and their Families in the UK. Sheffield Hallam University Research, 2016 - The incidence and prevalence of Parkinson’s in the UK. Clinical Practice Research Datalink Summary report 2018.
Market Size (1/2)
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Current PD drug market expected to grow at 11.1% CAGR.Market Size (2/2)
PD Drug Sales 7 Major Markets ($ Bn)
0
2
5
7
9
2012 2016 2022 2026
0.8
0.60.60.4
1.8
1.511.2
6.2
2.11.51
US EU5 JPN
• 2016-2026 CAGR = 11.1% • New US approvals expected in coming years • Levodopa represents 38% of the total market
Sources: • Global Data. Parkinson’s Disease Global Drug Forecast and Market Analysis to 2022. June 2015. • Global Data. Parkinson’s Disease Global Drug Forecast and Market Analysis to 2026. May 2018. (1) 7MM: US, Germany, UK, France, Spain, Italy and Japan.
16%
33%51%
US EU5 Jap
14%
25% 60%
2016
2026
Levodopa Sales 7MM ($ Bn)
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !13
Compared to alternatives, Lipea® promises to be the best add-on therapy for the foreseeable future.
Sources: https://www.drugs.com/sfx/amantadine-side-effects.html, https://www.addextherapeutics.com/en/news-and-events/press-releases/addex-dipraglurant-positive-phase-2-data-pd-lid-published-leading-peer-reviewed-journal-movement-disorder-society/, https://www.ncbi.nlm.nih.gov/pubmed/25669730, https://www.ncbi.nlm.nih.gov/pubmed/20803300, https://www.ncbi.nlm.nih.gov/pubmed/26990766, https://www.drugs.com/sfx/ketamine-side-effects.html
Amantadine Gocovri
(Approved)
Dipraglurant ADX48621 (Phase II)
Eltoprazine (Phase II)
Levetiracetam (Phase II)
AQW051 (Phase II)
Ketamine (Discovery)
High Medium Medium Low Low Low Low
High Low Low Low Low Low Low
Low High Medium Medium High Medium High
Low None Medium Medium Medium High Medium
All Only Late Stage n/a n/a Only Late
Stage n/a Only Late Stage
Dyskinesia Reduction
Side Effects
Translational Risk
Patients Addressed
1
2
3
4
5
(Pre-Clinical)
Movement Recovery Enhancement
Competitive Landscape (1/2)
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Alternative treatments are only recommended in 10% of cases, and are highly invasive and expensive.
Competitive Landscape (2/2)
Sources: Okun M. et al. Guide to Deep Brain Stimulation Therapy. US National Parkinson Foundation, 2017. Soulas T et al. Attempted and completed suicides after subthalamic nucleus stimulation for Parkinson's disease. J Neurol Neurosurg Psychiatry. 2008;79(8):952. Epub 2008 Apr 10 Doshi P et al. Depression leading to attempted suicide after bilateral subthalamic nucleus stimulation for Parkinson's disease. Mov Disord. 2002;17(5):1084.
- Implanted electrodes 12cm into the brain.
- Surgery cost: up to $ 100K.
- May increase the risk for suicide
- Direct infusion via a tube inserted in the intestines.
- Only for advanced cases.
- Costs $ 10K to $ 70K / year, plus surgery
Deep Brain Stimulation (DBS)
Levodopa/Carbidopa Intestinal Gel (LCIG)
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An industry-experienced team.Team
Industry Experience:Scientific Background:
CEO Pablo Inones
Operations Ruben Henriquez, PhD
Medical Research Fernando Rodriguez de Fonseca, PhD
Drug Development Tina Garyantes, PhD
Media & Marketing Andy Maier
Bio-Engineering Alcides Nicastro, PhD
Pharmacology Rafael de la Torre Fornell, PhD
Pre-Clinical Research José Lanciego, PhD
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What if you had the opportunity to take a good look at the path ahead before starting your trek?
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !17
Lipea® allows for a rapid, less expensive, early proof of concept*.
* Pre-IND efficacy assessment as anti-dyskinetic and motor enhancer. ** Investigational New Drug (IND) *** Food for Special Medical Purpose (FSMP) as defined by the European Food Safety Authority (EFSA); and Medical Food (MF) as defined by the US Food and Drug Administration (FDA)
Clinical Development Strategy (1/3)
Rare opportunity to perform early efficacy and safety studies in patients before requesting IND** status.
Active Molecule Features
• Meets criteria for FSMP and MF*** • Endogenous molecule • Therapeutic level within normal physiological range • Excellent safety profile, no adverse effects detected to date • Extensively studied mechanism of action
• Ingredients already in commercial useDelivery System
Preliminary proof of concept will make pharmaceutical clinical development more efficient and less risky.
Why
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !18
Current financing round founds our preliminary proof of concept* studies in humans.
Target Validation
Lead Optimization
Chemistry Process
Pre-Clinical Development
Pilot Studies in Humans*
Clinical Phases I & IIDiscoveryDiscovery NDA
Approval
Successfully completed Current Stage
Clinical Phase III
Market
Clinical Development Strategy (2/3)
Objectives: • Preliminary proof of concept* in humans • Translational de-risking of clinical
development • Abbreviate later clinical studies • Gather human data on safety and efficacy
in a cost-effective manner • GLP-GMP preparation for IND
Endpoints: • Patient Quality of Life: Motor Functionality • Pharmacokinetics • Bioavailability • Toxicology / safety
* Pre-IND efficacy assessment as anti-dyskinetic and motor enhancer.
© NOS Life Sciences Corp. - Proprietary and Confidential - Do not distribute !19
Significantly lower investment to complete Clinical Development*.Clinical Development Strategy (3/3)
Investment to first proof of concept**: € 1M € 37 M
* When compared with typical new chemical entity clinical development. ** Pre-IND efficacy assessment as anti-dyskinetic and motor enhancer.
1st human efficacy data
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Recent transactions in the Parkinson’s drug space.
Movement Recovery Enhancement
# Date Asset Developer Buyer Indication/ target Stage Value
1 2018 Jul Eltoprazine® / 5HT1a/b agonist Elto Pharma (US) Amaranthus (US) Levodopa add-on therapy to
reduce dyskinesia Phase II $316M
2 2018 Jul Dipaglurant® / mGLUR5 antagonist
Addex(Switzerland) Stock Appreciation Levodopa add-on therapy to
reduce dyskinesia Phase II €270M
3 2018 Mar Foliglurax® (mGLUR4 agonist)
Prexton Ther. (Netherlands- Switzerland)
Lundbeck A/S (Denmark)
Levodopa add-on therapy to reduce Off period Ph.II € 905 M
4 2017 Aug MEDI1341 anti-alpha synuclein AstraZeneca (UK) Takeda (Japan) Reduce synuclein-induced
neurodegeneration Ph. I €400M
5 2017 Aug Gocovri®: extended release Amantadine Adamas (US) Stock Appreciation Levodopa add-on therapy to
reduce dyskinesia Approved ~$ 450M
6 2016 Aug APL-130277: sublingual Apomorphine Cynapsus (USA) Sunovion (USA) Levodopa add-on therapy to
reduce Off periodPivotal ph.II/III $624M
7 2016 Jan Tozadenant® A2a antagonist Biotie (Finland) Acorda (USA) Levodopa add-on therapy to
reduce Off period Ph.III $363M
Market Dynamics
*
Cases based on new formulations of known drugs.*
*
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Out-license or trade-sale deals will provide attractive exit opportunities to investors.
Exit Opportunities
NDA Approval
Lipea® presents the perfect opportunity to boost an aging multi-billion-dollar portfolio of the leading pharmaceutical companies.
Company Value** (€):
Time (years): Today +1.5 +1.5 +2.5
6.5 M 58 M 142 M 600 M
+ 1
1.2 B
Current Stage Next StagesCompleted
Clinical Phase I & II
Discovery & Pre-Clinical Development
Clinical Phase III
Market
Pilot Studies in Humans*
* pre-IND efficacy assessment as Anti-dyskinetic and Motor enhancer. ** Standard valuation method: clinic-probability-discounted net present value over 3-X peak-sales terminal value.
•
OpEx22%
Payroll28%
R&D50%
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A € 1M investment expected to yield 6x return in 1½ years.Current Financing Round
Round Values
Capital Requirement € 1 M
Estimated Pre-Money Valuation € 6.5 M
Time Covered 18 months
Estimated Valuation after completion of current stage. € 58 M
Key Use of Proceeds
Standard valuation method: clinic-probability-discounted net present value over 3-X peak-sales terminal value.
www.noslifesciences.com USA: 1241 Canary Island Dr., Weston, FL (33327) Spain: Avenida de Carlos Haya, 75, Málaga, Andalusia (29010)